[Structural study of substituted benzamides with antidopaminergic D-2 activity. Comparison with orthopramides with 5HT-3 antiserotoninergic profile].

Crystallographic results coupled with theoretical calculations, NMR analyses, and molecular graphic design have been used to investigate the three-dimensional structures of different Na(+)-dependent D-2 antagonists. Three putative pharmacophoric elements, a nitrogen lone pair, a phenyl ring, and a carbonyl moiety, are similarly oriented in all these compounds. Moreover, a stereoelectronic model can be deducted from the molecular electrostatic potential maps. Conversely, for Na(+)-independent analogs, the two latter pharmacophoric elements play a subordinate role, but two electron regions are systematically localized on the other side of the molecule. The three pharmacophoric elements of the Na(+)-dependent D-2 antagonists have been identified in the 5HT-3 antiserotoninergic drugs, but only in terms of chemical functions.